Sodium hydride → 3-Oxo-4-(2-pyrrolidin-1-yl-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 655517Notes

Reaction equation

HRID 655517 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][NH:13][C:12](=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[CH2:18][CH2:19][N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1.Cl.ClCCN1CCCC1>CN(C)C(=O)C.C1(C)C=CC=CC=1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([CH2:18][CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[C:12](=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 816691-(2-Chloroethyl)pyrrolidineHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 669995983-Oxo-4-(2-pyrrolidin-1-yl-ethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 42%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent

Procedure

Sodium hydride (55% dispersion in mineral oil, 1.96 g, 45 mmol) was added portionwise at room temperature to a solution of 3-oxo-piperazine-1-carboxylic acid tert-butyl ester (6.01 g, 30.0 mmol) in N,N-dimethylacetamide (150 ml), then a solution of 1-(2-chloroethyl)-pyrrolidine in toluene [prepared from commercially available 1-(2-chloroethyl)-pyrrolidine hydrochloride (16.1 g, 94.5 mmol) by partitioning between toluene (70 ml) and 1 M aq. sodium hydroxide solution (70 ml) and drying of the organic layer with Na2SO4] was added dropwise. The reaction mixture was stirred at room temperature for 16 h, then heated at 75° C. for 80 min. After cooling, the reaction mixture was partitioned between diethyl ether and sat. aq. sodium hydrogen-carbonate solution. The organic layer was dried (Na2SO4) and evaporated. Crystallization of the residue from diethyl ether afforded the title compound (3.74 g, 42%). White solid, MS (ISP)=298.2 (M+H)+.

Workup

  1. customby partitioning between toluene (70 ml) and 1 M aq. sodium hydroxide solution (70 ml)
  2. dry with materialdrying of the organic layer with Na2SO4]
  3. additionwas added dropwise
  4. temperatureheated at 75° C. for 80 min
  5. temperatureAfter cooling
  6. customthe reaction mixture was partitioned between diethyl ether and sat. aq. sodium hydrogen-carbonate solution
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. customevaporated
  9. customCrystallization of the residue from diethyl ether

Sources & evidence

ORD record
ord-7cfc7c7e5e9d46fc922a636130eefd14
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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